Abstract
A major clinical challenge in Gaucher disease is the early and presymptomatic discrimination of type 2 (acute neuronopathic) from milder type 1 and type 3 Gaucher patients to enable appropriate management and counseling. Although most patients with Gaucher disease do not have skin abnormalities, a subset of patients with severe type 2 Gaucher disease display ichthyosiform skin. Analogous findings occur in the skin of type 2 (null allele) Gaucher mice. Ultrastructural and functional studies of epidermis from these mice reveal that glucocerebrosidase is required to generate functionally competent membranes for normal epidermal barrier function. We have extended our studies by examining the epidermal lipid content and ultrastructure in all three types of Gaucher patients. Only the type 2 Gaucher patients, some of whom had clinical ichthyosis, demonstrated an increased ratio of epidermal glucosylceramide to ceramide as well as extensive ultrastructural abnormalities, including the persistence of incompletely processed lamellar body-derived contents throughout the stratum corneum interstices. These epidermal alterations may provide a means for early differentiation of type 2 Gaucher disease.
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Abbreviations
- HPTLC:
-
high performance thin layer chromatography
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Acknowledgements
The authors gratefully acknowledge the technical assistance of Dr. Cindy McKinney, Lester Carmon, and Debbie Crumrine. The anatomic pathology services of Detroit Children's Hospital, University of Rochester Medical Center, and the laboratories of Children's and Presbyterian University Hospitals of the University of Pittsburgh are also acknowledged. The clinical assistance of Dr. Judith Westman of Columbus Children's Hospital is also greatly appreciated.
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Supported in part by National Institutes of Health Grants AR 19098 and 39448, and the Medical Research Service, Veterans Administration.
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Sidransky, E., Fartasch, M., Lee, R. et al. Epidermal Abnormalities May Distinguish Type 2 from Type 1 and Type 3 of Gaucher Disease. Pediatr Res 39, 134–141 (1996). https://doi.org/10.1203/00006450-199601000-00020
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DOI: https://doi.org/10.1203/00006450-199601000-00020
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